Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, most commonly involving the skin, joints and kidneys. Immunologic abnormalities, a genetic predisposition, viruses and other environmental agents have been implicated in contributing to the pleiotropic phenotypic characteristics of SLE. It is the aim of the present study to determine if persistent sites of DNA damage caused by deficient DNA repair processes may be involved in the development of pathogenic immune complexes and neoplasia in patients with SLE. Cellular survival assays will be utilized to determine the ultraviolet (UV) light sensitivity of SLE skin fibroblasts. UV light has been selected as our primary DNA damaging agent since sunlight is the most common environmental cause of SLE exacerbations. Having determined their sensitivity to UV light, the DNA repair capacity of SLE cells will be investigated utilizing autoradiographic and biochemical assays. We will also conduct experiments designed to confirm the existence of a photoactivatable, lowmolecular weight clastogenic factor in the serum of lupus patients. It has been proposed that such a factor may be responsible for an increased level of chromosome aberrations in SLE lymphocytes. Having isolated the clastogenic factor and characterized its activation by UV light, we will explore the possibility that it causes DNA lesions which are not properly repaired by SLE cells. Survival assays will be performed to measure the sensitivity of SLE cells to irradiated and non-irradiated clastogenic factors. We believe a significant contribution towards understanding SLE will evolve from our studies into the hypothesis that persistent DNA damage in coexistence with immunoregulatory dysfunctions may be responsible for certain clinical features of SLE. It is hoped that a better understanding of the disease mechanisms will provide new insights into management of SLE.